The inhibitor of ribonuclease isolated from the human placenta will be submitted to partial sequence analysis in order to facilitate structural studies of its interaction with the enzyme. Such data will be prerequisite for derivatization experiments to define the segments of the chain that interact with RNase. The information will also be needed for interpretation of studies on the X-ray crystallography of the enzyme:inhibitor complex. Antibodies to the inhibitor will be used in cytological experiments to examine the intracellular distribution of the protein. The aim is to ascertain the possible modes by which the inhibitor may affect the process of protein biosynthesis. The ratio of RNase to inhibitor will be studied in the mouse submaxillary gland, which is known to show diurnal variation in the rate of protein synthesis. The RNase inhibitors will be isolated from different cellular souces, such as liver and brain, to permit comparative studies on the inhibitors from different tissues. Species variations will also be examined. The 2'.3'-cyclic nucleotide 3'-phosphodiesterase, which has now been found both in brain and in retina will be subjected to cytological studies with the antibody thereto. Dimeric derivatives of pancreatic ribonuclease will be prepared for study of their uptake by transformed cells and for cytotoxicity. One derivative will be -S-S- cross-linked in order to learn whether potential -SH groups in the monomer affect cell uptake. Preliminary experiments are being conducted on the use of basic proteins, such as RNase dimers, as carriers of tumorostatic drugs.